HIV-1 infection is a significant health problem among intravenous drug users (IVDUs). The prevalence of infection is rising in this group and their sexual partners; who both may play a critical role in spreading the infection to heterosexual populations who are not users of illicit drugs. Most of the studies on HIV-I infection among IVDUs are based on serological markers to define infection. The sensitivity of this method is reasonable among individuals who have well developed patterns of antibodies against HIV-I. The polymerase chain reaction (PCR) technique is being used in our laboratory to improve the diagnosis of HIV-I infection. We have used PCR to identify individuals who show evidence of HIV-I infection, but lack detectable serological markers within a cohort of 1200 gay/bisexual men. Our preliminary data in studying seroconverters indicates that homosexual/bisexual man become PCR positive for HIV-1 prior to seroconversion by ELISA or Western blot. We propose to use the same PCR techniques in a prospective study of a cohort of HIV-1 antibody negative active IVDUs to determine the prevalence and incidence of HIV-I PCR positive individuals. Within a 12 month period we anticipate the enrollment and repeated screening of 1,000 HIV-l antibody negative IVDUs; we estimate that of these, a total number of 100 PCR positive individuals will be identified and followed up at six month intervals for up to three years. The information obtained from PCR methodology together with the data from on-going conventional virology and immunology studies will provide extremely valuable information on the early stages of natural history of HIV-I viral infections and the possibility of infectivity of PCR positive, serologically negative individuals. The study will provide biological materials to permit molecular studies of the mechanisms which underlie the latency phase of infection.